Agios Pharmaceuticals, Inc. announced that The Lancet Oncology has published data from its global Phase III ClarIDHy study of Tibsovo (ivosidenib) in previously treated cholangiocarcinoma patients with an isocitrate dehydrogenase 1 (IDH1) mutation . The study met its primary endpoint, demonstrating a statistically significant improvement in progression-free survival (PFS) in patients randomized to Tibsovo compared with placebo patients. The safety profile observed in the study was consistent with previously published data. Data from this study were previously presented at the European Society for Medical Oncology Congress (ESMO), held in September 2019 in Barcelona, Spain.
ClarIDHy Phase III Trial : The ClarIDHy trial is a global, randomized Phase III trial in previously treated IDH1-mutant cholangiocarcinoma patients who have documented disease progression following one or two systemic therapies in the advanced setting. Patients were randomized 2:1 to receive either single-agent Tibsovo 500 mg once daily or placebo with crossover to Tibsovo permitted at the time of documented radiographic progression per RECIST 1.1. At the time of the primary analysis, a total of 185 patients were randomized, with 124 patients in the Tibsovo arm and 61 patients in the placebo arm. Thirty-five patients randomized to placebo (57.4%) crossed over to open-label Tibsovo upon radiographic disease progression and unblinding.
Results of the study were as follows : Median PFS for patients randomized to TIBSOVO® was 2.7 months compared to 1.4 months with placebo (hazard ratio [HR]=0.37; 95% CI [0.25, 0.54], one-sided p<0·0001) as assessed by independent radiology review. The estimated PFS rate was 32% at six months and 22% at 12 months for patients randomized to Tibsovo, while no patients randomized to placebo were free from progression beyond six months as of the data cut-off. The most common treatment-emergent adverse events (AEs) of any grade for the 121 patients who received Tibsovo were nausea (36%), diarrhea (31%) and fatigue (26%). Less than third of patients experienced serious AEs in either arm (30% of 121 who received Tibsovo versus 22% of 59 patients who received placebo). The most common Grade 3 or worse AE in both treatment groups was ascites (nine [7%] of 121 patients who received Tibsovo and four [7%] of 59 patients who received placebo). Patients randomized to placebo experienced a significantly greater decline in physical functioning from baseline compared to patients randomized to ivosidenib on the first day of their second 28-day treatment cycle based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Physical Functioning subscale scores (p=0.0059). Tibsovo is not approved in any country for the treatment of patients with previously treated advanced IDH1-mutant cholangiocarcinoma.
See- Cited in Scopus: “Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase III study”- Ghassan K Abou-Alfa, Teresa Macarulla, Milind M Javle, Robin K Kelley, Sam J Lubner, Jorge Adeva, and others The Lancet Oncology. Published: May 13, 2020.